4JYT

Crystal Structure of Matriptase in complex with Inhibitor

4JYT の概要

• エントリーDOI: 10.2210/pdb4jyt/pdb
• 関連するPDBエントリー: 4jz1 4jzi
• 分子名称: Suppressor of tumorigenicity 14 protein, 4,4'-[{3-[(naphthalen-2-ylsulfonyl)amino]pyridine-2,6-diyl}bis(oxy)]dibenzenecarboximidamide (3 entities in total)
• 機能のキーワード: matriptase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane ; Single-pass type II membrane protein : Q9Y5Y6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27016.36

構造登録者

Subramanya, H.S.,Ravi, B.C.,Ashok, K.N.,Chakshusmathi, G.,Ramesh, K.S. (登録日: 2013-04-01, 公開日: 2014-03-19, 最終更新日: 2024-11-13)

主引用文献

Goswami, R.,Mukherjee, S.,Wohlfahrt, G.,Ghadiyaram, C.,Nagaraj, J.,Chandra, B.R.,Sistla, R.K.,Satyam, L.K.,Samiulla, D.S.,Moilanen, A.,Subramanya, H.S.,Ramachandra, M.
Discovery of Pyridyl Bis(oxy)dibenzimidamide Derivatives as Selective Matriptase Inhibitors
ACS MED.CHEM.LETT., 4:1152-1157, 2013

PubMed Abstract: Matriptase belongs to trypsin-like serine proteases involved in matrix remodeling/degradation, growth regulation, survival, motility, and cell morphogenesis. Herein, we report a structure-based approach, which led to the discovery of sulfonamide and amide derivatives of pyridyl bis(oxy)benzamidine as potent and selective matriptase inhibitors. Co-crystal structures of selected compounds in complex with matriptase supported compound designing. Additionally, WaterMap analyses indicated the possibility of occupying a distinct pocket within the catalytic domain, exploration of which resulted in >100-fold improvement in potency. Co-crystal structure of 10 with matriptase revealed critical interactions leading to potent target inhibition and selectivity against other serine proteases.

PubMed: 24900621
DOI: 10.1021/ml400213v

実験手法

X-RAY DIFFRACTION (2 Å)